|
|
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result sql = Stimulation of ES-cell-derived cardiomyogenesis and neonatal cardiac cell proliferation by reactive oxygen species and NADPH oxidase.
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char = ;code = 32
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char = ;code = 32
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char = g;code = 103
char = l;code = 108
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char = c;code = 99
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char = N;code = 78
char = M;code = 77
char = P;code = 80
char = G;code = 71
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char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = E;code = 69
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char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = R;code = 82
char = O;code = 79
char = S;code = 83
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = u;code = 117
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char = e;code = 101
char = d;code = 100
char = ;code = 32
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char = p;code = 112
char = r;code = 114
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char = s;code = 115
char = s;code = 115
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char = o;code = 111
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char = ;code = 32
char = t;code = 116
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char = e;code = 101
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = c;code = 99
char = -;code = 45
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
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char = g;code = 103
char = e;code = 101
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char = e;code = 101
char = s;code = 115
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char = e;code = 101
char = n;code = 110
char = c;code = 99
char = o;code = 111
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
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char = p;code = 112
char = h;code = 104
char = a;code = 97
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char = a;code = 97
char = c;code = 99
char = t;code = 116
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char = n;code = 110
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char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
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char = M;code = 77
char = H;code = 72
char = C;code = 67
char = ,;code = 44
char = ;code = 32
char = M;code = 77
char = L;code = 76
char = C;code = 67
char = 2;code = 50
char = a;code = 97
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char = ;code = 32
char = M;code = 77
char = L;code = 76
char = C;code = 67
char = 2;code = 50
char = v;code = 118
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = A;code = 65
char = N;code = 78
char = P;code = 80
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = c;code = 99
char = r;code = 114
char = i;code = 105
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = G;code = 71
char = A;code = 65
char = T;code = 84
char = A;code = 65
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char = 4;code = 52
char = ,;code = 44
char = ;code = 32
char = N;code = 78
char = k;code = 107
char = x;code = 120
char = -;code = 45
char = 2;code = 50
char = .;code = 46
char = 5;code = 53
char = ,;code = 44
char = ;code = 32
char = M;code = 77
char = E;code = 69
char = F;code = 70
char = 2;code = 50
char = C;code = 67
char = ,;code = 44
char = ;code = 32
char = D;code = 68
char = T;code = 84
char = E;code = 69
char = F;code = 70
char = -;code = 45
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = B;code = 66
char = M;code = 77
char = P;code = 80
char = -;code = 45
char = 1;code = 49
char = 0;code = 48
char = .;code = 46
char = ;code = 32
char = D;code = 68
char = u;code = 117
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = E;code = 69
char = S;code = 83
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = N;code = 78
char = A;code = 65
char = D;code = 68
char = P;code = 80
char = H;code = 72
char = ;code = 32
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = N;code = 78
char = o;code = 111
char = x;code = 120
char = -;code = 45
char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = N;code = 78
char = o;code = 111
char = x;code = 120
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = N;code = 78
char = o;code = 111
char = x;code = 120
char = -;code = 45
char = 4;code = 52
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = c;code = 99
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = R;code = 82
char = O;code = 79
char = S;code = 83
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = N;code = 78
char = o;code = 111
char = x;code = 120
char = -;code = 45
char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = N;code = 78
char = o;code = 111
char = x;code = 120
char = -;code = 45
char = 4;code = 52
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = 2;code = 50
char = 2;code = 50
char = -;code = 45
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = x;code = 120
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = 4;code = 52
char = 7;code = 55
char = -;code = 45
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = x;code = 120
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = p;code = 112
char = 6;code = 54
char = 7;code = 55
char = -;code = 45
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = x;code = 120
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = N;code = 78
char = o;code = 111
char = x;code = 120
char = -;code = 45
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = N;code = 78
char = o;code = 111
char = x;code = 120
char = -;code = 45
char = 4;code = 52
char = ;code = 32
char = m;code = 109
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = f;code = 102
char = e;code = 101
char = e;code = 101
char = d;code = 100
char = -;code = 45
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = w;code = 119
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = R;code = 82
char = O;code = 79
char = S;code = 83
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = N;code = 78
char = A;code = 65
char = D;code = 68
char = P;code = 80
char = H;code = 72
char = ;code = 32
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = p;code = 112
char = h;code = 104
char = e;code = 101
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char = y;code = 121
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = o;code = 111
char = d;code = 100
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = u;code = 117
char = m;code = 109
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = l;code = 108
char = o;code = 111
char = r;code = 114
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = D;code = 68
char = P;code = 80
char = I;code = 73
char = );code = 41
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = o;code = 111
char = c;code = 99
char = y;code = 121
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = s;code = 115
char = h;code = 104
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = R;code = 82
char = O;code = 79
char = S;code = 83
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = i;code = 105
char = o;code = 111
char = m;code = 109
char = y;code = 121
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = E;code = 69
char = S;code = 83
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = O;code = 79
char = u;code = 117
char = r;code = 114
char = ;code = 32
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = o;code = 111
char = f;code = 102
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char = n;code = 110
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char = o;code = 111
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = E;code = 69
char = S;code = 83
char = -;code = 45
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
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char = r;code = 114
char = i;code = 105
char = v;code = 118
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char = d;code = 100
char = ;code = 32
char = c;code = 99
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char = r;code = 114
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = c;code = 99
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
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char = i;code = 105
char = n;code = 110
char = v;code = 118
char = o;code = 111
char = l;code = 108
char = v;code = 118
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = R;code = 82
char = O;code = 79
char = S;code = 83
char = -;code = 45
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = s;code = 115
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char = g;code = 103
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
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char = c;code = 99
char = a;code = 97
char = s;code = 115
char = c;code = 99
char = a;code = 97
char = d;code = 100
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = w;code = 119
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
char = o;code = 111
char = l;code = 108
char = v;code = 118
char = e;code = 101
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = N;code = 78
char = A;code = 65
char = D;code = 68
char = P;code = 80
char = H;code = 72
char = ;code = 32
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = i;code = 105
char = o;code = 111
char = v;code = 118
char = a;code = 97
char = s;code = 115
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = E;code = 69
char = S;code = 83
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
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result sql = After birth the proliferation of cardiac cells declines, and further growth of the heart occurs by hypertrophic cell growth. In the present study the cell proliferation capacity of mouse embryonic stem (ES) cells versus neonatal cardiomyocytes and the effects of reactive oxygen species (ROS) on cardiomyogenesis and cardiac cell proliferation of ES cells was investigated. Low levels of hydrogen peroxide stimulated cardiomyogenesis of ES cells and induced proliferation of cardiomyocytes derived from ES cells and neonatal mice, as investigated by nuclear translocation of cyclin D1, downregulation of p27(Kip1), phosphorylation of retinoblastoma (Rb), increase of Ki-67 expression and incorporation of BrdU. The observed effects were blunted by the free radical scavengers vitamin E and 2-mercaptoglycin (NMPG). In ES cells ROS induced expression of the cardiac-specific genes encoding alpha-actin, beta-MHC, MLC2a, MLC2v and ANP as well as the transcription factors GATA-4, Nkx-2.5, MEF2C, DTEF-1 and the growth factor BMP-10. During differentiation ES cells expressed the NADPH oxidase isoforms Nox-1, Nox-2 and Nox-4. Treatment of cardiac cells with ROS increased Nox-1, Nox-4, p22-phox, p47-phox and p67-phox proteins as well as Nox-1 and Nox-4 mRNA, indicating feed-forward regulation of ROS generation. Inhibition of NADPH oxidase with diphenylen iodonium chloride (DPI) and apocynin abolished ROS-induced cardiomyogenesis of ES cells. Our data suggest that proliferation of neonatal and ES-cell-derived cardiac cells involves ROS-mediated signalling cascades and point towards an involvement of NADPH oxidase in cardiovascular differentiation of ES cells.
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result sql = Stimulation of ES-cell-derived cardiomyogenesis and neonatal cardiac cell proliferation by reactive oxygen species and NADPH oxidase.
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char = l;code = 108
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char = A;code = 65
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char = a;code = 97
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char = w;code = 119
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char = l;code = 108
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char = ;code = 32
char = t;code = 116
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char = t;code = 116
char = r;code = 114
char = a;code = 97
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char = s;code = 115
char = c;code = 99
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char = t;code = 116
char = i;code = 105
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char = f;code = 102
char = a;code = 97
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char = s;code = 115
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char = G;code = 71
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char = A;code = 65
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char = F;code = 70
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char = D;code = 68
char = T;code = 84
char = E;code = 69
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char = i;code = 105
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char = c;code = 99
char = e;code = 101
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char = l;code = 108
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char = s;code = 115
char = e;code = 101
char = d;code = 100
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char = t;code = 116
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char = e;code = 101
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char = N;code = 78
char = A;code = 65
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char = P;code = 80
char = H;code = 72
char = ;code = 32
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char = f;code = 102
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char = o;code = 111
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char = 1;code = 49
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char = 2;code = 50
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char = 4;code = 52
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char = a;code = 97
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char = l;code = 108
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char = -;code = 45
char = 1;code = 49
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char = 4;code = 52
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char = o;code = 111
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char = R;code = 82
char = O;code = 79
char = S;code = 83
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char = g;code = 103
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char = I;code = 73
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char = i;code = 105
char = b;code = 98
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char = N;code = 78
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char = P;code = 80
char = H;code = 72
char = ;code = 32
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char = t;code = 116
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char = o;code = 111
char = f;code = 102
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char = N;code = 78
char = A;code = 65
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char = P;code = 80
char = H;code = 72
char = ;code = 32
char = o;code = 111
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char = e;code = 101
char = l;code = 108
char = l;code = 108
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result sql = After birth the proliferation of cardiac cells declines, and further growth of the heart occurs by hypertrophic cell growth. In the present study the cell proliferation capacity of mouse embryonic stem (ES) cells versus neonatal cardiomyocytes and the effects of reactive oxygen species (ROS) on cardiomyogenesis and cardiac cell proliferation of ES cells was investigated. Low levels of hydrogen peroxide stimulated cardiomyogenesis of ES cells and induced proliferation of cardiomyocytes derived from ES cells and neonatal mice, as investigated by nuclear translocation of cyclin D1, downregulation of p27(Kip1), phosphorylation of retinoblastoma (Rb), increase of Ki-67 expression and incorporation of BrdU. The observed effects were blunted by the free radical scavengers vitamin E and 2-mercaptoglycin (NMPG). In ES cells ROS induced expression of the cardiac-specific genes encoding alpha-actin, beta-MHC, MLC2a, MLC2v and ANP as well as the transcription factors GATA-4, Nkx-2.5, MEF2C, DTEF-1 and the growth factor BMP-10. During differentiation ES cells expressed the NADPH oxidase isoforms Nox-1, Nox-2 and Nox-4. Treatment of cardiac cells with ROS increased Nox-1, Nox-4, p22-phox, p47-phox and p67-phox proteins as well as Nox-1 and Nox-4 mRNA, indicating feed-forward regulation of ROS generation. Inhibition of NADPH oxidase with diphenylen iodonium chloride (DPI) and apocynin abolished ROS-induced cardiomyogenesis of ES cells. Our data suggest that proliferation of neonatal and ES-cell-derived cardiac cells involves ROS-mediated signalling cascades and point towards an involvement of NADPH oxidase in cardiovascular differentiation of ES cells.
Publication: J. Cell. Sci. 2007 Mar 1 ;120(Pt 5)::885-94.
Publication Date: 2007 Mar 1
Study Author(s): Buggisch, Martina;Ateghang, Bernadette;Ruhe, Carola;Strobel, Catrin;Lange, Sabine;Wartenberg, Maria;Sauer, Heinrich;
Institution: Department of Physiology, Justus-Liebig-University Giessen, Aulweg 129, 35392 Giessen, Germany.
Shortcut link to this study:
Publication Date: 2007 Mar 1
Study Author(s): Buggisch, Martina;Ateghang, Bernadette;Ruhe, Carola;Strobel, Catrin;Lange, Sabine;Wartenberg, Maria;Sauer, Heinrich;
Institution: Department of Physiology, Justus-Liebig-University Giessen, Aulweg 129, 35392 Giessen, Germany.
Shortcut link to this study:
After birth the proliferation of cardiac cells declines, and further growth of the heart occurs by hypertrophic cell growth. In the present study the cell proliferation capacity of mouse embryonic stem (ES) cells versus neonatal cardiomyocytes and the effects of reactive oxygen species (ROS) on cardiomyogenesis and cardiac cell proliferation of ES cells was investigated. Low levels of hydrogen peroxide stimulated cardiomyogenesis of ES cells and induced proliferation of cardiomyocytes derived from ES cells and neonatal mice, as investigated by nuclear translocation of cyclin D1, downregulation of p27(Kip1), phosphorylation of retinoblastoma (Rb), increase of Ki-67 expression and incorporation of BrdU. The observed effects were blunted by the free radical scavengers vitamin E and 2-mercaptoglycin (NMPG). In ES cells ROS induced expression of the cardiac-specific genes encoding alpha-actin, beta-MHC, MLC2a, MLC2v and ANP as well as the transcription factors GATA-4, Nkx-2.5, MEF2C, DTEF-1 and the growth factor BMP-10. During differentiation ES cells expressed the NADPH oxidase isoforms Nox-1, Nox-2 and Nox-4. Treatment of cardiac cells with ROS increased Nox-1, Nox-4, p22-phox, p47-phox and p67-phox proteins as well as Nox-1 and Nox-4 mRNA, indicating feed-forward regulation of ROS generation. Inhibition of NADPH oxidase with diphenylen iodonium chloride (DPI) and apocynin abolished ROS-induced cardiomyogenesis of ES cells. Our data suggest that proliferation of neonatal and ES-cell-derived cardiac cells involves ROS-mediated signalling cascades and point towards an involvement of NADPH oxidase in cardiovascular differentiation of ES cells.
PMID: 17298980
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